Anti-inflammatory, but not lipid-lowering, activity of hepatocyte PPARα improves atherosclerosis in Ldlr- deficient mice

ABSTRACT: Atherogenic dyslipidemia and chronic inflammation appear strongly associated with residual cardiovascular disease (CVD) risk. Peroxisome proliferator-activated receptor α (PPARα) agonists, which exert both triglyceride-lowering and anti-inflammatory properties, are potential therapeutic candidates to target residual CVD risk. However, CVD outcome studies with these drugs have yielded mixed results for currently unclear reasons. Thus, we performed single-nucleus RNA sequencing (snRNA-seq) to better understand the hepatic-specific molecular actions of PPARα and their distal effects on atherosclerotic plaque development. Hepatic PPARα activation limits a pro-inflammatory phenotype in hepatocytes and reduces leukocyte recruitment. This study highlights a non-lipid, anti-inflammatory mechanism of hepatic PPARα with implications for cardiovascular disease modulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE295990 | GEO | 2025/05/28

REPOSITORIES: GEO